Pre-clinical development of Listeria-based nanovaccines as immunotherapies for solid tumours: insights from melanoma. (1st February 2019)

• Record Type: Journal Article
• Authors: Terán-Navarro, Hector; Calderon-Gonzalez, Ricardo; Salcines-Cuevas, David; García, Isabel; Marradi, Marco; Freire, Javier; Salmon, Erwan; Portillo-Gonzalez, Mar; Frande-Cabanes, Elisabet; García-Castaño, Almudena; Martinez-Callejo, Virginia; Gomez-Roman, Javier; Tobes, Raquel; Rivera, Fernando; Yañez-Diaz, Sonsoles; Álvarez-Domínguez, Carmen
• Is Part Of: Oncoimmunology. Volume 8:Number 2(2019)
• Publication Date: 2019-02-01
• Subjects: Listeria -- melanoma -- nanoparticles -- immunotherapy -- therapeutic vaccination; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1541534
• Languages: English
• ISSNs: 2162-402X

Abstract

ABSTRACT: Gold glyconanoparticles loaded with the listeriolysin O peptide 91–99 (GNP-LLO91-99 ), a bacterial peptide with anti-metastatic properties, are vaccine delivery platforms facilitating immune cell targeting and increasing antigen loading. Here, we present proof of concept analyses for the consideration of GNP-LLO91-99 nanovaccines as a novel immunotherapy for cutaneous melanoma. Studies using mouse models of subcutaneous melanoma indicated that GNP-LLO91-99 nanovaccines recruite and modulate dendritic cell (DC) function within the tumour, alter tumour immunotolerance inducing melanoma-specific cytotoxic T cells, cause complete remission and improve survival. GNP-LLO91-99 nanovaccines showed superior tumour regression and survival benefits, when combined with anti-PD-1 or anti-CTLA-4 checkpoint inhibitors, resulting in an improvement in the efficacy of these immunotherapies. Studies on monocyte-derived DCs from patients with stage IA, IB or IIIB melanoma confirmed the ability of GNP-LLO91-99 nanovaccines to complement the action of checkpoint inhibitors, by not only reducing the expression of cell-death markers on DCs, but also potentiating DC antigen-presentation. We propose that GNP-LLO91-99 nanovaccines function as immune stimulators and immune effectors and serve as safe cancer therapies, alone or in combination with other immunotherapies.